Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal Cell recruitment

作     者：Silva, Andreia M. Almeida, Maria I. Teixeira, Jose H. Maia, Andre F. Calin, George A. Barbosa, Mario A. Santos, Susana G. 

作者机构：i3S - Instituto de Investigação e Inovação em Saúde Porto Portugal. INEB - Instituto de Engenharia Biomédica Universidade do Porto Porto Portugal. Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto Porto Portugal. IBMC - Instituto de Biologia Molecular e Celular Universidade do Porto Porto Portugal. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas USA. Center for RNA Interference and Non-Coding RNAs The University of Texas MD Anderson Cancer Center Houston Texas USA. i3S - Instituto de Investigação e Inovação em Saúde Porto Portugal. susana.santos@ineb.up.pt. INEB - Instituto de Engenharia Biomédica Universidade do Porto Porto Portugal. susana.santos@ineb.up.pt. 

出 版 物：《SCIENTIFIC REPORTS》 (科学报告)

年 卷 期：2017年第7卷第1期

页      面：1667-1667页

核心收录：

学科分类：12[管理学] 1201[管理学-管理科学与工程(可授管理学、工学学位)] 08[工学] 

基　　金：Norte Portugal Regional Operational Programme (NORTE), under the PORTUGAL Partnership Agreement, through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000012] FCT-Fundacao para a Ciencia e a Tecnologia [SFRH/BD/85968/2012, SFRH/BPD/91011/2012, SFRH/BD/112832/2015] NIH/NCI grants [1UH2TR00943-01] Fundação para a Ciência e a Tecnologia [SFRH/BD/85968/2012, SFRH/BD/112832/2015, SFRH/BPD/91011/2012] Funding Source: FCT 

摘      要：Orchestration of bone repair processes requires crosstalk between different cell populations, including immune cells and mesenchymal stem/stromal cells (MSC). Extracellular vesicles (EV) as mediators of these interactions remain vastly unexplored. Here, we aimed to determine the mechanism of MSC recruitment by Dendritic Cells (DC), hypothesising that it would be mediated by EV. Primary human DC-secreted EV (DC-EV), isolated by ultracentrifugation, were characterized for their size, morphology and protein markers, indicating an enrichment in exosomes. DC-EV were readily internalized by human bone marrow-derived MSC, without impacting significantly their proliferation or influencing their osteogenic/chondrogenic differentiation. Importantly, DC-EV significantly and dose-dependently promoted MSC recruitment across a transwell system and enhanced MSC migration in a microfluidic chemotaxis assay. DC-EV content was analysed by chemokine array, indicating the presence of chemotactic mediators. Osteopontin and matrix metalloproteinase-9 were confirmed inside EV. In summary, DC-EV are naturally loaded with chemoattractants and can contribute to cell recruitment, thus inspiring the development of new tissue regeneration strategies.